Scientists identify potential new target for disrupting mosquito reproduction

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A longstanding mystery in mosquito biology has been solved, opening a potential new path for controlling mosquitoes and the diseases they spread. For decades, scientists believed that juvenile hormone, a chemical signal essential for mosquito reproduction, needed two different receptors to work: one inside the cell and another on its surface. The internal receptor was identified years ago, but the second remained elusive.

Now, researchers from Virginia Tech have shown that one protein was doing both jobs all along. In a study published in the Proceedings of the National Academy of Sciences, the team found that the known receptor, called Methoprene-tolerant, or MET, operates in two locations.

"This allows juvenile hormone to coordinate both rapid and long-term responses, giving mosquitoes a precise way to control reproduction," said Jinsong Zhu, professor of biochemistry in the College of Agriculture and Life Sciences and lead investigator of the study. "By understanding that process more clearly, we can begin to identify new targets for controlling mosquitoes."

The research focused on the yellow fever mosquito, Aedes aegypti, a mosquito species known for spreading diseases including dengue, Zika, and yellow fever.

A new role for a protein essential to reproduction

Juvenile hormone acts as a signal that tells female mosquitoes when to begin producing eggs. It works by binding to a protein called MET inside the cell, where it switches on genes needed for egg development.

In the study, researchers observed that some of that same protein also works on the cell membrane, activating additional signal pathways that help eggs mature.

Together, these two layers help the hormone control when and how eggs are produced.

"These two layers can reinforce each other or pull in different directions, giving mosquitoes very precise control over reproduction," said Zhu, who is also affiliated faculty in the Fralin Life Sciences Institute.

When Zhu's team disrupted either role of MET, mosquitoes were unable to produce eggs normally, and reproduction dropped sharply. The finding shows both roles are necessary for egg production.

"Female mosquitoes have to carefully manage energy and nutrients to produce eggs, and if that process is disrupted, reproduction is reduced," Zhu said. "That makes this system an important point of control we can begin to study more closely."

A new path toward mosquito control

Diseases spread by mosquitoes, including dengue, Zika, and yellow fever, affect hundreds of millions of people worldwide each year, with dengue alone causing an estimated 100 million to 400 million infections annually.

Most insecticides kill mosquitoes by targeting their nervous systems. But over time, mosquitoes can develop resistance to these chemicals, making them less effective and driving the need for new approaches.

This study points to a different strategy—targeting the biological processes that allow mosquitoes to reproduce.

"Right now, most commercial insecticides that target this pathway focus on a single receptor," Zhu said. "If insects become resistant, those tools lose effectiveness. Identifying additional targets within the same pathway could help address that challenge."

By showing that one protein carries out two distinct functions, the study identifies new regulatory nodes in the reproductive process that could be targeted to disrupt mosquito reproduction.

"Our goal is not just to control mosquitoes, but to find targets that are specific to mosquitoes and reduce the impact on beneficial insects," Zhu said.

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A discovery that may extend beyond mosquitoes

Juvenile hormone is found across many insect species, and early interest from other research groups suggests the same mechanism could be more widespread. If confirmed, that could open new avenues for studying—and potentially managing—other insect species, including agricultural pests.

"It's exciting to see other labs beginning to test whether this mechanism exists in other insect species," Zhu said. "That tells us the discovery may have broader significance."

Zhu's team members are now working to understand how the MET protein moves to the cell's surface and what other molecules help control its activity. They are also testing whether blocking the protein's action on the cell membrane alone could stop mosquitoes from reproducing without affecting other important processes.

The work builds on long-term research in Zhu's lab focused on understanding how hormonal signaling controls mosquito reproduction. By mapping these pathways, his team aims to identify new molecular targets that could be used to suppress mosquito populations or limit disease transmission.

"Understanding mosquito biology at the molecular level is essential if we want to develop more effective and environmentally responsible control strategies," Zhu said.

Publication details

Wenhao Zhao et al, Membrane-localized MET engages PVR to mediate extranuclear juvenile hormone signaling in Aedes aegypti, Proceedings of the National Academy of Sciences (2025). DOI: 10.1073/pnas.2516796122

Journal information: Proceedings of the National Academy of Sciences

Key concepts

molecular biologypest controlPointy MosquitoBiomolecular & subcellular processes

Provided by Virginia Tech